Lung cancer patients that harbor oncogenic mutations in BRAF are treated with targeted therapies and present tumor responses that are mostly partial, ultimately followed by resistance to therapy within about 10 months. The very limited knowledge on the molecular mechanisms that promote resistance to therapy in these patients has hampered the development of subsequent therapeutic strategies to improve their survival. Besides, the current lack of pertinent BRAF-mutant NSCLC pre-clinical models has hindered the study precision medicine pre-clinical approaches to tackle therapy resistance in this context. Based on long histories of collaboration, scientific expertise and unique institutional resources, we recently initiated the BOLERO consortium, which assembles basic researchers, translational scientists and thoracic oncologists that are actively engaged in innovative and multidisciplinary lung cancer research, in high-level research institutes and some top academic medical centers in Europe. The goal of BOLERO is to integrate the scientific and clinical expertise currently available among individual partner institutes, to translate it into discoveries that might improve the survival of BRAF-mutant lung cancer patients. In this research program, we propose to capitalize on our current synergy 1) to pre-clinically model the impact of genomic alterations in effectors of the MAPK and PI3K pathways in sensitivity to BRAF-targeted therapies; 2) to generate clinically relevant patient-derived models, as well as knock-in mouse models of BRAF-mutant NSCLC, that will serve to identify therapeutic rationales to revert resistance to BRAF-targeted therapies; and 3) to assess the potential role of epithelial-to-mesenchymal transition and lineage plasticity in resistance to targeted therapies, by transcriptomic and immunohistochemistry analyses of tumor samples from BRAF-driven NSCLC. With this research program, we will identify molecular vulnerabilities that might subsequently translate into therapeutic rationales to delay or revert the emergence of resistance to therapy in BRAF-mutant lung cancer patients. To increase our competitiveness for the World Cancer Research grants, we plan to utilize the potential MRSEI ANR funding 1) to establish the Consortium and Data/Material Transfer Agreements to ensure the integration of patient samples and the associated clinical information; 2) to hold scientific meetings to define the scientific and economic strategies for the implementation of the research program, promote the coherence of the group and stimulate collaboration among the investigators; and 3) develop a web-based, integrated database to gather the molecular and clinical information of the tumour samples collected at the participating institutions of the Consortium, as well as the patient-derived models generated by the BOLERO investigators. This joint strategy streamline research efforts, decrease costs and facilitate connections with the communities of lung cancer research and clinical management. To our knowledge, BOLERO is the first consortium in the lung cancer community dedicated to study BRAF-mutant NSCLC. Overall BOLERO will promote the discovery of precision medicine approaches to prolong the survival of BRAF-mutant lung cancer patients.

Lifestyle factors of the patient (e.g. smoking, hazardous alcohol drinking and malnutrition) are proven to be independent risk factors negatively impacting health outcome in the perioperative process. Evidence suggests that the implementation of intensive lifestyle intervention programs can significantly reduce the post-surgery complication risk and rehabilitation time . However, implementation of and compliance to such programs are today poor. In addition, possibilities to optimize the patients’ mental and physical state throughout the perioperative process are insufficient. LIVE INCITE aims to move beyond the current state of general information being provided about risks and post-surgery activities, to translating statistics and data to individual-specific information, making the individual plan “real” for the patient. We believe it is possible to leverage f i existing and new data, best practice behavioral change concepts, intuitive and easy-to-use user experience, modern communication and collaboration channels to integrate not only patients and care providers but also the patient’s family and friends, and new technology for continuous monitoring of and feedback on patient activities related to her defined plan. But, no matter which concepts and solutions the market will suggest, sustainability and scalability (related to the likely changing needs and pre-requisites of the specific procurer as well as the dissemination in and uptake from a European-wide procurer community) has to be enforced through principles related to interoperability, open architecture, and use of international standards. Through its consortia including specialized care hospitals, academia, patient organizations as well as collaboration and innovation platforms the project has the critical mass of knowledge to reach a truly innovative solution together with the supply side.

In recent years, the majority of the world's Critical Infrastructures CIs evolved to become more flexible, cost efficient and able to offer better services and conditions for business opportunities. Towards this evolution, CIs and companies offering CI services had to adopt many of the recent advances of the Information and Communication Technologies (ICT) field. This adaptation however, was rather hasty and without thorough evaluation of its impact on security. The result was to leave CIs vulnerable to a who the new set of threats and attacks that impose high levels of risk to the public safety, economy and welfare of the population. In so far, the main approach to protect CIs is to handle them as comprehensive entities and offer them a complete solution for their overall infrastructures and systems (IT&OT departments). However Complete CI protection solutions exist in the form of individual products from individual companies. These products integrate only and tools/solutions designed by the same company, thus offering limited technical solutions. The main aim of CIPSEC is to create a unified security framework that orchestrates state-of-the-art heterogeneous security products to offer high levels of protection in IT (information technology) and OT (operational technology) departments of CIs. As part of this framework CIPSEC will offer a complete security ecosystem of additional services that can support the proposed technical solutions to work reliably and at professional quality. These services include vulnerability tests and recommendations, key personnel training courses, public-private partnerships (PPPs) forensics analysis, standardization and protection against cascading effects. All solutions and services will be validated in three pilots performed in three different CI environments (transportation, health, environment). CIPSEC will also develop a marketing strategy for optimal positioning of its solutions in the CI security market.

TALK© is a communication tool which aims to guide multi-professional clinical teams learning and improving quality of patient care and patient safety together. It is a simple and practical approach to multi-professional structured feedback and debriefing, to be used after unplanned learning events in clinical environments. Debriefing is the process of an individual or team formally reflecting on their performance after a particular task, a shift or a critical event (World Health Organisation 2009). TALK proposes an easy way to guide a constructive conversation between team members whenever new insights might be learnt from clinical experience. This includes cases or sessions in which things went well but also near misses and untoward events. Patient safety is far too often threatened by unidentified system flaws, poor practices, weaknesses in team communication and lack of appropriate action after critical events. The relevance of a culture of safety and communication is emphasized by WHO advocating debriefing in its Human Factors review, 2009. This RISE project will consist of three phases; firstly secondees will contribute to parallel implementation processes in specified units across the 3 participating countries and will undertake research to better understand the benefits of structured debriefing, communication and organisational culture. Secondly, using the data generated from the research study, further training materials will be developed and translated to support the wider deployment of the TALK tool. Thirdly, the TALK tool will be widely disseminated as a structured debriefing tool and implemented across and beyond all participating partners and its impact will be assessed.